19-17555811-G-T

Position:

chr19-17555811-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024656.4(COLGALT1):c.98G>T(p.Gly33Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000516 in 1,260,602 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00044 ( 4 hom. )

Consequence

COLGALT1
NM_024656.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.38

Variant links:

Genes affected

COLGALT1 (HGNC:26182): (collagen beta(1-O)galactosyltransferase 1) The protein encoded by this gene is one of two enzymes that transfers galactose moieties to hydroxylysine residues of collagen and mannose binding lectin. This gene is constitutively expressed and encodes a soluble protein that localizes to the endoplasmic reticulum. [provided by RefSeq, Dec 2015]

COLGALT1 links:

COLGALT1 (HGNC:):

COLGALT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009623677).

BP6

Variant 19-17555811-G-T is Benign according to our data. Variant chr19-17555811-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1971578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00106 (161/151576) while in subpopulation NFE AF= 0.000782 (53/67804). AF 95% confidence interval is 0.000614. There are 0 homozygotes in gnomad4. There are 106 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COLGALT1	NM_024656.4 linkuse as main transcript	c.98G>T	p.Gly33Val	missense_variant	1/12	ENST00000252599.9	NP_078932.2	Q8NBJ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COLGALT1	ENST00000252599.9 linkuse as main transcript	c.98G>T	p.Gly33Val	missense_variant	1/12	1	NM_024656.4	ENSP00000252599.3		Q8NBJ5

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

161

AN:

151468

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0102

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000782

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00135

AC:

AN:

11118

Hom.:

AF XY:

0.00124

AC XY:

AN XY:

7274

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0133

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000442

AC:

490

AN:

1109026

Hom.:

Cov.:

AF XY:

0.000419

AC XY:

222

AN XY:

530364

show subpopulations

Gnomad4 AFR exome

AF:

0.0000436

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000163

Gnomad4 FIN exome

AF:

0.00865

Gnomad4 NFE exome

AF:

0.000287

Gnomad4 OTH exome

AF:

0.000406

GnomAD4 genome

AF:

0.00106

AC:

161

AN:

151576

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

106

AN XY:

74082

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0102

Gnomad4 NFE

AF:

0.000782

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000900

Hom.:

Bravo

AF:

0.000302

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 24, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 04, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.018

Eigen

Benign

-0.012

Eigen_PC

Benign

-0.0047

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.48

M_CAP

Pathogenic

0.44

MetaRNN

Benign

0.0096

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.3

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.61

REVEL

Benign

0.24

Sift

Benign

0.35

Sift4G

Benign

0.39

Polyphen

0.94

Vest4

0.43

MVP

0.81

MPC

0.36

ClinPred

0.14

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over